Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9921423 | European Journal of Pharmacology | 2005 | 12 Pages |
Abstract
Cyclosporin A is an immunosuppressor that prolongs graft survival but its use is limited by cardiotoxicity. The effects of cyclosporin A on several functional and biological characteristics were thus evaluated in rat cardiomyocytes in normal conditions and in a substrate-free, hypoxia-reoxygenation model of ischemia-reperfusion. Cyclosporin A (100 and 1000 ng/ml) did not induce cardiocytotoxicity in basal conditions. Simulated ischemia gradually decreased and then blocked the spontaneous electromechanical activity. Cyclosporin A at 100 and 1000 ng/ml permitted the maintenance of electromechanical functions that were abolished in control cells. Cyclosporin A also improved the post-“ischemic” functional recovery. Cyclosporin A reduced the “ischemia”-induced lactate dehydrogenase and troponine I releases and the successive rises in heat shock protein mRNA observed after “ischemia” and reoxygenation. Moreover, cyclosporin A improved the resumption of the mitochondrial function. To conclude, cyclosporin A displayed a direct, pleiotropic protection of isolated cardiomyocytes against physiological, metabolic, structural and stress signaling changes induced by ischemia-reperfusion mimicked in vitro.
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Authors
Sandrine Bès, David Vandroux, Cindy Tissier, Lisa Devillard, Amandine Brochot, Etienne Tatou, Laurence Duvillard, Luc Rochette, Pierre Athias,